TGF-beta 1 down-regulates induced expression of both class II MHC and B7-1on primary murine renal tubular epithelial cells

Background. We examined the immunomodulatory effects of transforming growth factor-beta 1 (TGF-beta 1) on the regulation of class II MHC and costimula tory molecule expression in a primary renal tubular epithelial cell line, c alled F1K. Methods. Class II major histocompatibility complex (MHC), class II transact ivator, B7-1, intercellular adhesion molecule-1 (ICAM-1) and interferon-gam ma (IFN-gamma) receptor beta chain were evaluated in untreated and cytokine -treated F1K by Northern hybridization analysis and flow cytometry. T cell activation studies were performed to assess TGF-beta 1-mediated effects on antigen presenting cell function of F1K. Results. Pretreatment of F1K with TGF-beta 1 markedly inhibited IFN-gamma-i nduced class II MHC expression, by both FAGS and Northern analysis. Total c lass II transactivator mRNA levels were also diminished by TGF-beta 1, indi cating that class II MHC modulation in F1K results from inhibition of this intermediate protein. As previous studies demonstrated that cotreatment of F1K cells with IFN-gamma + lipopolysaccharide (LPS) induces B7-1, we evalua ted the potential regulatory effects of TGF-beta 1 exposure on B7-1 express ion. Our studies revealed that B7-1 mRNA and cell-surface expression in IFN -gamma + LPS-treated F1K were decreased by TGF-beta 1 pretreatment. Functio nal studies evaluating TGF-beta 1-mediated effects were performed with IFN- gamma + LPS-treated F1K and MR1.3, a nephritogenic CD4(+) Th2 clone derived from kidneys of animals with autoimmune glomerulonephritis. Interleukin (I L)-4 production assays demonstrated activation of MR1.3 by IFN-gamma + LPS- treated cells, but not by IFN-gamma + LPS-treated cells previously exposed to TGF-beta 1, indicating that TGF-pl-mediated inhibition of class II MHC a nd B7-1 expression alters the antigen presenting cell function of F1K, Conclusions. These studies describe the proscriptive influence of TGF-beta 1 on class II MHC and B7-1 expression in renal tubular epithelial cells. Su ch findings indicate that TGF-beta 1 alters the antigen presenting cell fun ction of renal tubular epithelial cells in vitro, and suggest a potential m echanism for immunosuppression of T cell-mediated renal immune responses in vitro.